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NCUEIR > College of Social Science and Physical Education > sh > Periodical Articles > Item 987654321/17857

Please use this identifier to cite or link to this item: http://ir.ncue.edu.tw/ir/handle/987654321/17857

Title:	Hypoxia induces BMP-2 Expression Via ILK, Akt, mTOR and HIF-1 Pathways in Osteoblasts
Authors:	Tseng, Wen-Pei;Yang, Shu-Ning;Lai, Chih-Ho;Tang, Chih-Hsin
Contributors:	運動健康所
Date:	2010-06
Issue Date:	2014-01-15T04:02:53Z
Publisher:	Wiley-Liss, Hoboken, NJ, ETATS-UNIS
Abstract:	It has been shown that hypoxia stimulation regulates bone formation, maintenance, and repair. Bone morphogenetic protein (BMP) plays important roles in osteoblastic differentiation and bone formation. However, the effects of hypoxia exposure on BMP-2 expression in cultured osteoblasts are largely unknown. Here we found that hypoxia stimulation increased mRNA and protein levels of BMP-2 by qPCR, Western blot and ELISA assay in osteoblastic cells MG-63, hFOB and bone marrow stromal cells M2-10B4. Integrin-linked kinase (ILK) inhibitor (KP-392), Akt inhibitor (1L-6-hydroxymethyl-chiro-inositol-2-[(R)-2-O-methyl-3-O-octadecylcarbonate]) or mammalian target of rapamycin (mTOR) inhibitor (rapamycin) inhibited the potentiating action of hypoxia. Exposure to hypoxia increased the kinase activity of ILK and phosphorylation of Akt and mTOR. Furthermore, hypoxia also increased the stability and activity of HIF-1 protein. The binding of HIF-1α to the HRE elements after exposure to hypoxia was measured by EMSA assay. Moreover, the use of pharmacological inhibitors or genetic inhibition revealed that both ILK/Akt and mTOR signaling pathway were potentially required for hypoxia-induced HIF-1α activation and subsequent BMP-2 up-regulation. Taken together, our results provide evidence that hypoxia enhances BMP-2 expression in osteoblasts by an HIF-1α-dependent mechanism involving the activation of ILK/Akt and mTOR pathways. J. Cell. Physiol. 223:810–818, 2010. © 2010 Wiley-Liss, Inc.
Relation:	Journal of Cellular Physiology, 223(3): 810-818
Appears in Collections:	[sh] Periodical Articles

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